/pdf/nccn-clinical-practice-guidelines-in-oncology-hepatobiliary-1kpacqqvi8.pdf

NCCN clinical practice guidelines in oncology: hepatobiliary cancers.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guerin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

/pdf/breast-cancer-version-3-2020-nccn-clinical-practice-2j1ac48n8w.pdf

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

BACKGROUND.

Data from randomized, controlled trials of zoledronic acid were retrospectively analyzed to assess the effect of pathologic fractures on survival in patients with malignant bone disease.



METHODS.

A Cox regression model was used to estimate the effect of fractures (time-dependent variable) on survival in patients with stage III multiple myeloma or bone metastases from solid tumors enrolled in 3 large trials. Patients were randomized to receive zoledronic acid, pamidronate, or placebo every 3–4 weeks for up to 24 months (prostate cancer, breast cancer, and multiple myeloma) or up to 21 months (lung and other solid tumors).



RESULTS.

A total of 3049 patients with multiple myeloma (n = 513), breast (n = 1130), prostate (n = 640), or lung cancer or other solid tumors (n = 766) were included in this analysis. Patients with multiple myeloma had the highest fracture incidence (43%), followed by breast (35%), prostate (19%), and lung cancer (17%). In all tumor types except lung, pathologic fracture was associated with a significant increase in risk of death, and breast cancer patients had the greatest increased risk. After adjustment for baseline characteristics, including performance status and prior skeletal complications, breast cancer patients who developed a pathologic fracture on study had a significant 32% increased risk of death relative to patients without a fracture (hazard ratio = 1.32; P 20% increased risk of death.



CONCLUSIONS.

These results suggest that fractures are associated with increased risk of death in patients with malignant bone disease. Therefore, preventing fractures is an important goal of therapy. Cancer 2007. © 2007 American Cancer Society.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.22991

Pathologic fractures correlate with reduced survival in patients with malignant bone disease.

Purpose To investigate the efficacy and safety of zoledronic acid for the treatment of bone metastases from breast cancer. Patients and Methods Women with bone metastases (N = 228) were randomly assigned to receive 4 mg zoledronic acid (n = 114) or placebo (n = 114) via 15-minute infusions every 4 weeks for 1 year. The primary efficacy end point was the skeletal-related event (SRE) rate ratio between treatment groups. An SRE was defined as pathologic fracture, spinal cord compression, and radiation or surgery to bone. Secondary end points included percentage of patients with at least one SRE, time-to-first SRE, and Andersen-Gill multiple-event analysis. Results The SRE rate ratio at 1 year (excluding HCM and adjusted for prior fracture) was 0.61 (permutation test; P = .027), indicating that zoledronic acid reduced the rate of SRE by 39% compared with placebo. The percentage of patients with at least one SRE (excluding HCM) was significantly reduced by 20% by zoledronic acid (29.8% v 49.6% for placebo; P =...

https://ascopubs.org/doi/pdf/10.1200/JCO.2005.05.116

Zoledronic Acid Significantly Reduces Skeletal Complications Compared With Placebo in Japanese Women With Bone Metastases From Breast Cancer: A Randomized, Placebo-Controlled Trial

https://doc.rero.ch/record/304136/files/mdm442.pdf

Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel

BACKGROUND
Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial.

METHODS
Overall, 1130 patients with breast carcinoma who had all types of bone metastases (osteolytic, mixed, or osteoblastic by radiology) were randomized to receive treatment with either 4 mg of Zol or 8 mg of Zol as a 15-minute infusion or 90 mg of Pam as a 2-hour infusion every 3–4 weeks for 12 months. A skeletal-related event (SRE) was defined as a pathologic fracture, spinal cord compression, radiotherapy, or surgery to bone.

RESULTS
Among all patients with BC, the proportion of those who had an SRE (primary endpoint) was comparable between treatment groups (43% of patients who received 4 mg of Zol vs. 45% of patients who received Pam). Among patients who had breast carcinoma with at least 1 osteolytic lesion (n = 528 patients), the proportion with an SRE was lower in the 4-mg Zol group compared with the Pam group (48% vs. 58%), but this did not reach statistical significance (P = 0.058). The time to first SRE was significantly longer in the 4-mg Zol group compared with the Pam group (median, 310 vs. 174 days; P = 0.013). Moreover, multiple-event analysis demonstrated significant further reductions in the risk of developing SREs over the reduction achieved with Pam (30% in the osteolytic subset [P = 0.010] and 20% for all patients with BC [P = 0.037]).

CONCLUSIONS
The current data indicate that treatment with 4 mg of Zol was more effective than 90 mg of Pam in reducing skeletal complications in a subset of patients with breast carcinoma who had at least 1 osteolytic lesion at study entry. Cancer 2004;100:36–43. © 2003 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.11892

Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion

Histiocytic medullary reticulosis (HMR) was originally defined as a neoplastic disorder. Some cases reported as HMR have been characterized by a systemic proliferation of mature histiocytes showing hemophagocytosis, bone marrow necrosis, pancytopenia, hepatitis, and coagulopathy. Clinically, these patients have fever and constitutional symptoms and often have hepatosplenomegaly and lymphadenopathy. Although there is a high mortality rate, this process appears to be reactive and has been associated with active viral infection. Similar cases have been briefly described that were associated with other agents or disease processes, but concomitant viral infections were not excluded. Three characteristic examples of this hemophagocytic syndrome that were associated with bacterial sepsis are described. Active infection by those viruses that have previously been associated with the syndrome was excluded. It appears that the hemophagocytic syndrome may be associated with various types of active disseminated infections.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819841215%2954%3A12%3C2968%3A%3AAID-CNCR2820541226%3E3.0.CO%3B2-4

Bacteria-associated hemophagocytic syndrome

Controversy exists regarding the efficacy of various treatment schedules and drug combinations for patients with multiple myeloma. Fifty‐three patients with this malignancy were evaluated. In a prospective program, 31 patients received an intermittent combination drug schedule using melphalan and prednisone, and the results were compared to a group of 22 patients, studied retrospectively, who had been treated with continuous cyclophosphamide or melphalan administered to hematologic tolerance. Objective response occurred in 74% of those receiving the intermittent combination regimen compared to a 41% response rate for those receiving continuous alkylating agents. Eight patients who relapsed while on continuous alkylators were switched to the intermittent combination regimen, and three responded. Morbidity was not increased with intermittent combination drug program.

https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%28197206%2929%3A6%3C1665%3A%3AAID-CNCR2820290634%3E3.0.CO%3B2-4

D. Gordon

Papers

Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion

Bacteria-associated hemophagocytic syndrome

Multiple myeloma--intermittent combination chemotherapy compared to continuous therapy.

P107 Zoledronic acid is superior to pamidronate in patients with breast cancer and multiple myeloma who are at high risk for skeletal complications

P104 Continuing benefit of zoledronic acid for the prevention of skeletal complications in breast cancer patients with bone metastases